Publications

BACKGROUND

Prioritizing interventions for patients with syphilis who are part of large or interconnected sexual networks may be high yield for partner services, and identifying venues named by patients with syphilis who report high numbers of partners may help identify such networks. In this analysis, we explore differences between interviewed patients with early syphilis regarding where they met sex partners.

METHODS

With a cross-sectional design, we examined the distribution of total reported sex partners from male index patients with early syphilis interviewed through the San Francisco Department of Public Health partner services program and the self-reported venues named as places they met sex partners. Based on the median number of total partners among male cases of syphilis who named each venue, we categorized venues into 3 levels of partner frequency: high (>15 partners reported), medium (6-15 partners reported), and low (<6 partners reported). Interviewed patients with early syphilis were then classified into these venue categories, and sociodemographic and risk behaviors from electronic medical records and interviews were compared using χ tests.

RESULTS

In 2011, 433 male patients with early syphilis named 32 venues. One hundred forty-three (32.3%) patients were categorized as high, 226 (51.0%) as medium, and 74 (16.7%) as low partner frequency venue users. Patients with early syphilis who reported meeting partners at high partner frequency venues were generally older, more likely to be white, have a previous syphilis infection, use methamphetamines in the previous year, and be HIV infected (all P < 0.05) compared with those who reported meeting partners at medium-frequency and low-frequency venues.

CONCLUSIONS

Venues where partners are met may be an appropriate proxy for network membership. Targeting additional resources, outreach, and services to clients who attend high-frequency venues may have a positive impact on syphilis prevention efforts.

BACKGROUND

The relationship between anemia and undiagnosed tuberculosis (TB) in patients living with HIV in sub-Saharan Africa is incompletely defined. We assessed the prevalence of TB among those with HIV-related anemia and evaluated new means of rapid TB diagnosis.

METHODS

Blood hemoglobin levels were measured in unselected antiretroviral treatment-naive patients in Cape Town, South Africa, and anemia was classified according to World Health Organization criteria. All patients were screened for TB by testing paired sputum samples using liquid culture (reference standard), fluorescence microscopy, and Xpert MTB/RIF. Urine samples were tested for lipoarabinomannan (LAM) using the Determine TB-LAM diagnostic assay.

RESULTS

Of 602 adults screened, 485 had complete results. Normal hemoglobin levels were found in 44.5% (n = 216) of patients, and mild, moderate, or severe anemia were present in 24.9% (n = 121), 25.4% (n = 123) and 5.2% (n = 25) of patients, respectively. Culture-confirmed pulmonary TB was diagnosed in 8.8% (19/216) of those without anemia compared with 16.5% (20/121), 26.0% (32/123), and 40.0% (10/25) among those with mild, moderate, or severe anemia, respectively (P < 0.001). Anemia was a strong independent predictor of TB. The sensitivities of diagnostic assays were much higher among those with moderate/severe anemia compared with those with no/mild anemia using sputum microscopy (42.9% vs 15.4%), urine LAM (54.8% vs 0%), sputum microscopy plus urine LAM (71.4% vs 15.4%), and sputum Xpert (73.8% vs 41.0%) (P < 0.01 for all).

CONCLUSIONS

A very high prevalence of undiagnosed TB was found in patients with moderate or severe anemia. Such patients should be prioritized for routine microbiological investigation using rapid diagnostic assays.

The management of latent tuberculosis infection (LTBI) most commonly consists of a nine-month course of isoniazid (INH) therapy and is complicated by low adherence and completion rates. The Latent Tuberculosis Initiative at the HAVEN Free Clinic was developed to provide LTBI treatment to an underserved, high-risk, foreign-born population. We conducted a retrospective chart review to evaluate the program. Of 39 patients enrolled, 26 (67%) successfully completed nine months of INH, eight (21%) discontinued, and five (12%) were lost to follow-up. Patients had a median of nine encounters during the course of treatment and mean self-reported medication adherence was 29/30 pills/month (96%). Median days-of-treatment was 273, 95, and 63 among completion, discontinuation, and lost to follow-up groups, respectively (p < .0001). There was one death in the program, related to a complication of a diagnostic procedure in a patient who had developed INH toxicity. These results are comparable to the most successful published programs (50-65% six-month completion rates), suggesting that student-run clinics serving high-risk populations may contribute to LTBI management and TB control efforts.

OBJECTIVE

Hostility is associated with adverse outcomes in patients with coronary heart disease (CHD). However, assessment tools used to evaluate hostility in epidemiological studies vary widely.

METHODS

We administered nine subscales of the Cook-Medley Hostility Scale (CMHS) to 656 outpatients with stable CHD between 2005 and 2007. We used Cox proportional hazards models to determine the association between each hostility subscales and all-cause mortality. We also performed an item analysis using logistic regression to determine the association between each CMHS item and all-cause mortality.

RESULTS

There were 136 deaths during 1364 person-years of follow-up. Four of nine CMHS subscales were predictive of mortality in age-adjusted analyses, but only one subscale (the seven-item Williams subscale) was predictive of mortality in multivariable analyses. After adjustment for age, sex, education, smoking, history of heart failure, diabetes, and high-density lipoprotein, each standard deviation increase in the Williams subscale was associated with a 20% increased mortality rate (hazard ratio = 1.20, 95% confidence interval = 1.00-1.43, p = .046), and participants with hostility scores in the highest quartile were twice as likely to die as those in the lowest quartile (hazard ratio = 2.00, 95% confidence interval = 1.10-3.65, p = .023).

CONCLUSIONS

Among nine variations of the CMHS that we evaluated, a seven-item version of the Williams subscale was the most strongly associated with mortality. Standardizing the assessment of hostility in future epidemiological studies may improve our understanding of the relationship between hostility and mortality in patients with CHD.

Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or imbalance of the immune system can lead to autoimmunity, and thus elucidation of normal tolerance mechanisms has led to identification of therapeutic targets for treating autoimmune disease. In the past 15 years, a number of disease-modifying monoclonal antibodies and genetically engineered biologic agents targeting the immune system have been approved, notably for the treatment of rheumatoid arthritis, inflammatory bowel disease and psoriasis. Although these agents represent a major advance, effective therapy for other autoimmune conditions, such as type 1 diabetes, remain elusive and will likely require intervention aimed at multiple components of the immune system. To this end, approaches that manipulate cells ex vivo and harness their complex behaviors are being tested in preclinical and clinical settings. In addition, approved biologic agents are being examined in combination with one another and with cell-based therapies. Substantial development and regulatory hurdles must be overcome in order to successfully combine immunotherapeutic biologic agents. Nevertheless, such combinations might ultimately be necessary to control autoimmune disease manifestations and restore the tolerant state.

RATIONALE

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary artery pressure, vascular remodeling, and ultimately right ventricular heart failure. PAH can have a genetic component (heritable PAH), most often through mutations of bone morphogenetic protein receptor 2, and idiopathic and associated forms. Heritable PAH is not completely penetrant within families, with approximately 20% concurrence of inactivating bone morphogenetic protein receptor 2 mutations and delayed onset of PAH disease. Because one of the treatment options is using prostacyclin analogs, we hypothesized that prostacyclin synthase promoter sequence variants associated with increased mRNA expression may play a protective role in the bone morphogenetic protein receptor 2 unaffected carriers.

OBJECTIVES

To characterize the range of prostacyclin synthase promoter variants and assess their transcriptional activities in PAH-relevant cell types. To determine the distribution of prostacyclin synthase promoter variants in PAH, unaffected carriers in heritable PAH families, and control populations.

METHODS

Polymerase chain reaction approaches were used to genotype prostacyclin synthase promoter variants in more than 300 individuals. Prostacyclin synthase promoter haplotypes' transcriptional activities were determined with luciferase reporter assays.

MEASUREMENTS AND MAIN RESULTS

We identified a comprehensive set of prostacyclin synthase promoter variants and tested their transcriptional activities in PAH-relevant cell types. We demonstrated differences of prostacyclin synthase promoter activities dependent on their haplotype.

CONCLUSIONS

Prostacyclin synthase promoter sequence variants exhibit a range of transcriptional activities. We discovered a significant bias for more active prostacyclin synthase promoter variants in unaffected carriers as compared with affected patients with PAH.